The purpose of the project is to gain insight into the biologic function of the platelet membrane and the structure/function relationship within the membrane. The eventual aim is to use this information pharmacologically to modify platelet response in disease states such as atherosclerosis, (strokes and heart attacks), and thromboembolic arterial disease. Adhesion is the initial platelet response to endothelial injury, yet it is the least-well studied of platelet functions. To date, we have successfully set up an adhesion assay for a biologic surface and are testing the requirements for adhesion. We have found that ADP, epinephrine and 5HT enhance adhesion, while fibrinogen and albumin do not enhance adhesion. The presence of divalent cations are required for adhesion. Some lyophilized preparations of Factor VIII enhance adhesion. We intend to test and purify Factor VIII preparations to make certain of their role in adhesion. Effects of prostaglandins and other inhibitors to adhesion will be tested. We are studying the mapping and association of platelet membrane functions with defined chemical groups in the platelet membrane. By using a polymer bound SH-group modifier, we can restrict all interaction to the external surface of the platelet membrane. PEG-PCMB has been found to alter only aggregation, not 5HT uptake and not the release reaction. We therefore conclude that the SH-group associated with aggregation is superficially located while those associated with 5HT uptake and the release reaction are deeper. Electrophoresis of PEG-PCMB treated platelet membranes show no change in the electrophoretic pattern. C14 PEG-PCMB attaches about 10 to the 5th power molecules to the platelet membrane. We intend to use the C14 label to find where the altered SH group migrates. We also intend to study the effect of PEG-PCMB on the shape change and adhesion.